The project has three main parts: (1) produce GLP-grade iPS cell lines and derived RPE from three AMD patients. Patient samples will be developed in to GLP-grade iPS cell line and differentiated into RPE using a xeno-free medium. We plan to perform this process using samples from at least three patients to demonstrate process consistency; (2) demonstrate pre-clinical safety of the clinical product (iPSC-RPE transplant). This work will be performed in immunocompromised animals. iPSC-RPE transplants developed in part 1 will be transplanted in the sub-retinal space to determine acute and chronic, local and systemic safety profile of transplants. Histological analysis of the eye and other organs will be performed at different time points to identify potential damage or tumor or teratoma caused by iPSC-RPE transplant; (3) demonstrate pre-clinical efficacy of the clinical product (iPSC-RPE transplant). We have optimized a surgical procedure for transplantation of iPSC-RPE sheet in pigs. This surgery is performed using a four-port vitrectomy, similar to the procedure performed in humans. After removing the vitreous, a sub-retinal bleb is created by injecting saline in between the photoreceptors and the RPE. A small cut is made in the retina to transplant the iPSC-RPE scaffold in the sub-retinal space. Sub-retinal bleb is flattened using a heavy liquid (perflourocarbon), which is eventually exchanged with a gas SF6. We are currently evaluating the efficacy of the transplant in pig models of RPE injury.